Ferroptosis: a new strategy for cardiovascular disease

Cardiovascular disease (CVD) is currently one of the prevalent causes of human death. Iron is one of the essential trace elements in the human body and a vital component of living tissues. All organ systems require iron for various metabolic processes, including myocardial and skeletal muscle metabolism, erythropoiesis, mitochondrial function, and oxygen transport. Its deficiency or excess in the human body remains one of the nutritional problems worldwide. The total amount of iron in a normal human body is about 3–5 g. Iron deficiency may cause symptoms such as general fatigue, pica, and nerve deafness, while excessive iron plays a crucial role in the pathophysiological processes of the heart through ferroptosis triggered by the Fenton reaction. It differs from other cell death modes based on its dependence on the accumulation of lipid peroxides and REDOX imbalance, opening a new pathway underlying the pathogenesis and mechanism of CVDs. In this review, we describe the latest research progress on the mechanism of ferroptosis and report its crucial role and association with miRNA in various CVDs. Finally, we summarise the potential therapeutic value of ferroptosis-related drugs or ferroptosis inhibitors in CVDs

NRF2 Plays a Critical Role in Both Self and EGCG Protection against Diabetic Testicular Damage

Activation of nuclear factor erythroid 2-related factor 2 (NRF2) has been found to ameliorate diabetic testicular damage (DTD) in rodents. However, it was unclear whether NRF2 is required for these approaches in DTD. Epigallocatechin gallate (EGCG) is a potent activator of NRF2 and has shown beneficial effects on multiple diabetic complications. However, the effect of EGCG has not been studied in DTD. The present study aims to explore the role of NRF2 in both self and EGCG protection against DTD. Therefore, streptozotocin-induced diabetic C57BL/6 wild type (WT) and Nrf2 knockout (KO) mice were treated in the presence or absence of EGCG, for 24 weeks. The Nrf2 KO mice exhibited more significant diabetes-induced loss in testicular weight and spermatozoa count, and increase in testicular apoptotic cell death, as compared with the WT mice. EGCG activated NRF2 expression and function, preserved testicular weight and spermatozoa count, and attenuated testicular apoptotic cell death, endoplasmic reticulum stress, inflammation, and oxidative damage in the WT diabetic mice, but not the Nrf2 KO diabetic mice. The present study demonstrated for the first time that NRF2 plays a critical role in both self and EGCG protection against DTD

Krill Oil Inhibits NLRP3 Inflammasome Activation in the Prevention of the Pathological Injuries of Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM), resulting in high mortality. Myocardial fibrosis, cardiomyocyte apoptosis and inflammatory cell infiltration are hallmarks of DCM, leading to cardiac dysfunction. To date, few effective approaches have been developed for the intervention of DCM. In the present study, we investigate the effect of krill oil (KO) on the prevention of DCM using a mouse model of DM induced by streptozotocin and a high-fat diet. The diabetic mice developed pathological features, including cardiac fibrosis, apoptosis and inflammatory cell infiltration, the effects of which were remarkably prevented by KO. Mechanistically, KO reversed the DM-induced cardiac expression of profibrotic and proinflammatory genes and attenuated DM-enhanced cardiac oxidative stress. Notably, KO exhibited a potent inhibitory effect on NLR family pyrin domain containing 3 (NLRP3) inflammasome that plays an important role in DCM. Further investigation showed that KO significantly upregulated the expression of Sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), which are negative regulators of NLRP3. The present study reports for the first time the preventive effect of KO on the pathological injuries of DCM, providing SIRT3, PGC-1α and NLRP3 as molecular targets of KO. This work suggests that KO supplementation may be a viable approach in clinical prevention of DCM

Antioxidative Effects of Natural Products on Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes and results in high mortality. It is therefore imperative to develop novel therapeutics for the prevention or inhibition of the progression of DCM. Oxidative stress is a key mechanism by which diabetes induces DCM. Hence, targeting of oxidative stress-related processes in DCM could be a promising therapeutic strategy. To date, a number of studies have shown beneficial effects of several natural products on the attenuation of DCM via an antioxidative mechanism of action. The aim of the present review is to provide a comprehensive and concise overview of the previously reported antioxidant natural products in the inhibition of DCM progression. Clinical trials of the antioxidative natural products in the management of DCM are included. In addition, discussion and perspectives are further provided in the present review

Differences in the treatment and control of hypertension in urban and rural residents of the northeastern region of the People’s Republic of China: a cross-sectional study

Background: Hypertension is a significant global public health problem and an important risk factor for cardiovascular diseases. We aimed to determine treatment and control rates of hypertension and to explore related risk factors by urban and rural areas. Methods: A cross-sectional survey of 14,956 participants (≥ 15 years) was conducted in Jilin Province, China from July 2014 to December 2015 using questionnaire forms and physical measurements. Results: Total rates of hypertension treatment, control, and controlled blood pressure among treated subjects were 31.7%, 8.8%, and 27.9% in the Jilin Province. Rates of hypertension treatment, control, and controlled blood pressure among treated subjects were 35.9%, 13.7%, and 38.3% in urban areas and 28.4%, 5.0%, and 17.5% in rural areas, respectively. Higher treatment of hypertension was associated with older age, female sex, other races (except Han), and higher body fat percentage in both areas. Among urban residents, higher education was additionally associated with higher treatment of hypertension; among rural residents, a family history of coronary artery disease and unemployment were associated with higher treatment of hypertension. Higher control of hypertension was associated with unemployment, married status, higher education, healthy body mass index, lower abdominal waist circumference, non-smoking status, and lower visceral adiposity index in urban residents; higher control of hypertension was associated with younger age in rural residents. Conclusion: Treatment and control rates of hypertension in urban and rural areas were lower than the national average; blood pressure control in patients taking antihypertensive drugs needs further improvement

Differences in prevalence of hypertension and associated risk factors in urban and rural residents of the northeastern region of the People's Republic of China: A cross-sectional study.

Hypertension is a significant global public health problem and recognized as an important risk factor for cardiovascular diseases. This study was designed to assess the current prevalence of hypertension and to explore risk factors associated with hypertension by urban and rural status to guide the prevention and control of hypertension in Jilin province.A multi-stage stratified random cluster sampling method was used to obtain data on hypertension, which was investigated by physical examination and face-to-face questionnaire in July 2014-December 2015. Sample data were analyzed by complex weighted statistical analysis to estimate blood pressure levels and prevalence of hypertension in the province. Multivariable logistic regression analysis was used to identify factors influencing hypertension rates.The prevalence of hypertension was significantly higher in rural areas than urban areas (25.93% versus 22.73%, respectively). The rates of hypertension known (46.7% versus 38.1%, respectively), control (13.7% versus 5.0%, respectively), and controlled among treated subjects (38.3% versus 17.5%, respectively) were higher in urban areas than in rural areas (all p < 0.001), while the treatment rate was not statistically significantly different between urban and rural areas (35.9% versus 28.4%, respectively). After adjusting for demographic covariates, hypertension prevalence in rural areas was still significantly greater than in urban areas (adjusted OR = 1.22; 95%CI: 1.10, 1.36; p < 0.001). Common risk factors for hypertension among urban and rural residents included older age; male; married; employed; less education; overweight/obese; greater abdominal waist circumference; family history of hypertension, stroke, or coronary heart disease; current smoker; alcohol consumption; higher visceral adiposity index; and higher body fat percentage.This study identified an increased risk for hypertension in rural regions of Jilin province, suggesting that rural hypertension screening and treatment guidelines should receive greater attention